We have obtained a molecular clone of integrated simian sarcoma virus (SSV) which possesses high-titered focus-forming activity. Analysis of our DNA clone revealed that SSV contains a nucleotide sequence, designated sis, which was derived from the genome of a New World primate. There is significant homology between sis and a uniquely represented nucleotide sequence found within the normal human genome. We have molecularly cloned the human analogue to sis and have begun to analyze its molecular and biologic properties. Efforts to search for involvement of this transforming retrovirus gene and its human analogue in naturlly occurring human tumors are in progress.